Esterification of Docosahexaenoic Acid Enhances Its Transport to the Brain and Its Potential Therapeutic Use in Brain Diseases

• Published in: Nutrients 2022-10, Vol.14 (21), p.4550
• Main Authors: Lo Van, Amanda, Bernoud-Hubac, Nathalie, Lagarde, Michel
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer's disease; Aspirin; Blood plasma; Blood-brain barrier; Brain; Brain diseases; Choline; Diet therapy; Dietary supplements; Docosahexaenoic acid; Esterification; Fatty acids; Fish oils; Health aspects; Heart; Liver; Lysophosphatidylcholine; lysophospholipids; Metabolites; Neurological diseases; Neuroprotection; Omega-3 fatty acids; Pharmaceutical research; Phospholipase D; Phospholipids; Physiological aspects; Physiology; Plasma; Review
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14214550

Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases.